Nuclear hormone receptors are ligand-activated transcription factors that regulate gene expression by interacting with specific DNA sequences typically upstream of their target genes. A two-step mechanism of action has been was proposed for these receptors based upon the observation of an inactive and an active state of the receptors. The first step involves activation through binding of the hormone; the second step consists of receptor binding to DNA and regulation of transcription.
After being bound by or interacting with its cognate ligand (e.g. a hormone), the nuclear hormone receptor typically binds to a hormone response element (HRE). A hormone response element is a specific DNA sequence that a hormone receptor recognizes with markedly increased affinity. The hormone receptor element typically contains two consensus hexameric half-sites. The identity of a response element generally resides in three features: the sequence of the base pairs in the half-site, the number of base pairs between the half-sites and the relative orientation of the two half-sites. Thus each receptor protein dimer that binds the DNA typically recognizes the sequence, spacing and orientation of the half-sites within their response element.
Binding of the response element by the nuclear receptor typically results in the up- or down-regulation of one or more genes under control of the response element. It is believed that, prior to this invention, this was the only way that nuclear hormone receptors, and specifically, steroid receptors functioned.